crossing96/oncoscreening huggingface dataset:
[Progress in treatment of PD-1/PD-L1 inhibitors for bladder cancer].	Because of the limited effect of traditional treatment methods such as surgical treatment, radiotherapy and chemotherapy,the emergence of immunotherapy has brought new hope for the treatment of patients with bladder cancer. As an immune checkpoint inhibitor, programmed death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) inhibitor has shown good anti-tumor activity and safety in the treatment of advanced bladder cancer, and has been recommended for advanced bladder cancer as second-line treatment by NCCN guidelines. PD-1/PD-L1 inhibitor for the treatment of bladder cancer has covered the first-line and second-line treatment, as well as maintenance therapy after first-line chemotherapy of locally advanced or metastatic bladder cancer, adjuvant and neoadjuvant therapy of muscle-invasive bladder cancer, treatment of high-risk non-muscle invasive bladder cancer failed by Bacille Calmette-Guérin vaccine perfusion, and bladder preservation therapy of muscle-invasive bladder cancer. Some of related studies have achieved certain results, and some are in progress, both of which need to be further examined. Maybe it can provide new guidance and ideas for clinical treatment of bladder cancer.	bladder
High S100A7 expression is associated with early muscle invasion and poor survival in bladder carcinoma.	Muscle-invasive bladder carcinoma (MIBC) accounts for 25% of newly diagnosed bladder carcinomas (BCs) and presents a high risk of progression and metastasis. This study aimed to identify reliable biomarkers associated with muscle invasion and prognosis to identify potential therapeutic targets for MIBC. Four gene datasets were downloaded from the Gene Expression Omnibus, and the integrated differentially expressed genes (DEGs) were then subjected to gene ontology (GO) terms and pathway enrichment analyses. Correlation analysis between the expression of the top-ranking DEGs and pathological T stages was performed to identify the genes associated with early muscle invasion. The corresponding prognostic values were evaluated, and co-expressed genes mined in the cBioPortal database were loaded into ClueGo in Cytoscape for pathway enrichment analysis. Using data mining from the STRING and TCGA databases, protein-protein interaction and competitive endogenous RNA networks were constructed. In total, 645 integrated DEGs were identified and these were mainly enriched in 26 pathways, including cell cycle, bladder cancer, DNA replication, and PPAR signaling pathway. S100A7 expression was significantly increased from the T2 stage and showed significantly worse overall survival and disease-specific survival in patients with BC. In total, 144 genes co-expressed with S100A7 in BC were significantly enriched in the IL-17 pathway. S100A7 was predicted to directly interact with LYZ, which potentially shows competitive binding with hsa-mir-140 to affect the expression of six lncRNAs in MIBC. In conclusion, high S100A7 expression was predicted to be associated with early muscle invasion and poor survival in patients with BC.	bladder
Safety, Efficacy, and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03.	PURPOSE: Immunotherapy offers a second-line option for patients with metastatic urothelial carcinoma (mUC) who failed standard therapy, but the biomarkers for predicting response remain to be explored. This study aims to evaluate the safety, efficacy, and correlative biomarker of toripalimab in patients with previously treated mUC. PATIENTS AND METHODS: Patients with mUC received toripalimab 3 mg/kg Q2W. Clinical response was assessed every 8 weeks by an independent review committee per RECIST v1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated. RESULTS: Among the intention-to-treat population (n = 151), 85% of the patients experienced treatment-related adverse event (TRAE) and 20% experienced grade 3 and above TRAE. The objective response rate (ORR) was 26% with a disease control rate (DCR) of 45%. The median duration of response, progression-free survival (PFS), and overall survival (OS) were 19.7 months [95% confidence interval (CI): 13.9-not estimable], 2.3 months (95% CI, 1.8-3.6), and 14.4 months (95% CI, 9.3-23.1), respectively. Both PD-L1(+) and TMB-high (10 mutations/Mb as the cutoff) patients had better ORR than PD-L1(-) patients (42% vs. 17%, P = 0.002) and TMB-low patients (48% vs. 22%, P = 0.014), respectively. The TMB-high group also showed better PFS (12.9 vs. 1.8 months, P < 0.001) and OS (not reached versus 10.0 months, P = 0.018) than the TMB-low group. CONCLUSIONS: Toripalimab has demonstrated encouraging clinical activity in the second-line treatment of mUC with a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.	bladder
Sugary drink consumption and risk of kidney and bladder cancer in Japanese adults.	Globally, sugary drinks are widely consumed, however, few epidemiologic studies have investigated the association between sugary drink consumption and risk of kidney and bladder cancer. We examined the association of sugary drinks with risk of kidney and bladder cancer in 73,024 participants from the Japan Public Health Center-based Prospective Study who reported no history of cancer. Sugary drink consumption was assessed using a validated food frequency questionnaire at study baseline (1995-1999). Individuals were followed to December 31, 2013. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs). During 1,069,815 person years of follow-up, 169 kidney cancer and 297 bladder cancer cases were documented. After adjusting for potential confounders, no greater risk of kidney and bladder cancer was observed. However, sugary drink consumption was positively associated with the risk of kidney cancer (HR for 100 ml/day increase in consumption was 1.11 [95% CI 1.01-1.22]) and bladder cancer (HR for 100 ml/d increase in consumption was 1.11 [95% CI 1.01-1.22]) among women after exclusion of cases diagnosed in the first three years of follow-up. In this large prospective cohort, consumption of sugary drinks was significantly associated with a small increase in hazard ratio for kidney and bladder cancer among women after exclusion of cases diagnosed within the first three years.	bladder
Response to Platinum-based Chemotherapy Rechallenge for Patients With Pembrolizumab-refractory Urothelial Carcinoma.	BACKGROUND: This study aimed to investigate the response to platinum-based chemotherapy rechallenge in patients with pembrolizumab-refractory urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed 14 patients with pembrolizumab-refractory urothelial carcinoma. Each patient received a regimen that they had not previously received (paclitaxel plus carboplatin in 10, gemcitabine plus docetaxel and carboplatin in four). Tumor response and adverse events were assessed. We evaluated overall survival from the chemotherapy rechallenge start date until death. RESULTS: The median overall survival was 11.2 months. The disease-control rate was 85.7%. Partial responses occurred in the metastases in lymph nodes in three (37.5%) patients, lung in one (25%), peritoneal in three (75%), and liver in three (100%). Neutropenia of grade ≥3 occurred in 13 (92.9%) patients. CONCLUSION: The activity of platinum-based chemotherapy rechallenge after pembrolizumab was maintained. Neutropenia was observed in most patients.	bladder
Survival Prediction by Baseline Systemic Immune-inflammation Index (SII) and its Changes During First-line Platinum-based Treatment in a Caucasian Population of Patients With Metastatic Urothelial Carcinoma (MUC).	BACKGROUND/AIM: Systemic immune-inflammation index (SII) predicts survival of patients with various malignancies. This study explored the prognostic value of SII in metastatic urothelial carcinoma (MUC) subjects. PATIENTS AND METHODS: We evaluated 181 consecutive MUC patients treated with first-line platinum-based therapy. Karnofsky performance status <80% and visceral metastasis were present in 18.2% and 46.4% of patients, respectively. SII was based on platelet × neutrophil/lymphocyte counts. Study population was dichotomized by median into high and low SII groups before the initiation of chemotherapy and at week 6. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: At median follow-up of 9.6 months, 174 patients experienced disease progression and 173 died. Patients with low SII at baseline and at week 6 had significantly better PFS (HR=0.58; p=0.0002 and HR=0.55; p<0.0001) and OS (HR=0.54; p<0.0001 and HR=0.54; p<0.0001) compared to patients with high SII. Independent prognostic value of SII was confirmed in a multivariate analysis. CONCLUSION: High SII before chemotherapy that persists at week 6 negatively affects survival. SII at baseline can be used in the stratification of patients within clinical trials and in clinical practice.	bladder
Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience.	INTRODUCTION: Neoadjuvant chemotherapy has become standard of care for cisplatin-eligible patients with muscle-invasive bladder cancer qualified to radical cystectomy, providing a modest increase in 5-year overall survival rate. Several regimens are being employed for neoadjuvant treatment, largely because of their efficacy in metastatic setting. There is however a scarcity of evidence on the optimal cytotoxic regimen for neoadjuvant chemotherapy. OBJECTIVES: We evaluated the efficacy of different protocols of neoadjuvant chemotherapy amongst patients who underwent radical cystectomy at our institution. METHODS: This is a single-center, retrospective, observational study including a cohort of 220 patients who underwent radical cystectomy between 2014 and 2020. The neoadjuvant chemotherapy cohort included 79 patients and was compared to the cohort of historical controls including 141 patients operated prior to routine administration of neoadjuvant chemotherapy and those who opted for upfront surgery. RESULTS: Administration of neoadjuvant chemotherapy decreased the risk of overall and cancer-specific mortality HR = 0.625 (95% CI 0.414-0.944), p = 0.025 and HR = 0.579 (95% CI 0.348-0.964), p = 0.036. Rates of downstaging, complete responses, lymph node metastasis, extravesical extension and positive surgical margins significantly favored neoadjuvant chemotherapy. Out of cytotoxic regimens, dose-dense MVAC and gemcitabine-cisplatin were similarly efficacious providing 46.9% and 50% of downstaging to <ypT2N0 respectively, including 30.6% and 25% of complete remissions. However, only dose-dense MVAC was associated with reduction of all-cause and cancer specific mortality risk HR = 0.385 (95% CI 0.214-0.691) p = 0.001 and HR = 0.336 (95% CI 0.160-0.703), p = 0.004 respectively. CONCLUSIONS: Our study implies that neoadjuvant chemotherapy with subsequent radical cystectomy provides significant improvement over upfront surgery in locoregional control and long-term prognosis of muscle-invasive bladder cancer. The urologic community should strive to maximize utilization of neoadjuvant chemotherapy, yet further research, including randomized control trials, is needed to validate superiority of dose-dense MVAC as the preferred regimen for cisplatin-eligible patients.	bladder
Prognostic value of preoperative neutrophil-to-lymphocyte ratio in histological variants of non-muscle-invasive bladder cancer.	PURPOSE: Many studies identified that the preoperative neutrophil-to-lymphocyte ratio (PNLR) was associated with patient prognosis in non-muscle-invasive bladder cancer (NMIBC). We hypothesized that PNLR could be prognostic in patients with histological variants of NMIBC (VH-NMIBC). MATERIALS AND METHODS: This retrospective study included patients with VH-NMIBC admitted at our center between January 2009 and May 2019. The best cut-off value of NLR was measured by the receiver operating characteristic curve and Youden index. The Kaplan-Meier method and Cox proportional hazard regression models were employed to evaluate the association between PNLR and disease prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: A total of 243 patients with VH-NMIBC were enrolled in our study. According to the Kaplan-Meier method results, patients with PNLR ≥2.2 were associated with poor RFS (p<0.001), PFS (p<0.001), CSS (p<0.001), and OS (p<0.001). Multivariable analyses indicated that PNLR ≥ 2.2 was an independent prognostic factor of RFS (hazard ratio [HR], 2.11; 95% confidence interval [CI, 1.57-1.83; p<0.001), PFS (HR, 2.34; 95% CI, 1.70-3.21; p<0.001), CCS (HR, 2.87; 95% CI, 1.96-4.18; p< 0.001), and OS (HR, 2.83; 95% CI, 1.96-4.07; p<0.001). CONCLUSIONS: This study identified that PNLR ≥2.2 was usually associated with a poor prognosis for patients with VH-NMIBC.	bladder
The benefit of a neoadjuvant instillation of chemotherapy in non-muscle invasive bladder cancer: Interim analysis of the PRECAVE randomized clinical trial.	OBJECTIVE: Although an immediate postoperative instillation of chemotherapy (IPOIC) after transurethral resection of bladder tumors (TURBT) is recommended for the prevention of recurrences of non-muscleinvasive bladder cancer (NMIBC), evidence shows there is an important compliance failure worldwide. We believe that an immediate neoadjuvant instillation of chemotherapy (INAIC) can act similarly, reducing the recurrence risk of NMIBC. Here we present the interim analysis of the PRECAVE clinical trial. MATERIAL AND METHODS: Patients with clinically diagnosed NMIBC were randomized to receive an INAIC with mitomycin C before TURBT (Group A) or to a control group with TURBT only (Group B). Primary end point was to compare the efficacy of an INAIC in the early recurrence-free survival (RFS). Secondary end points were: RFS in patients who did not receive adjuvant treatments, toxicity, and feasibility. RESULTS: A total of 124 patients with Ta/T1 G1-G3NMIBC were included in the initial analysis (Group A:64, Group B: 60). Demographics, risk classification, complications, and adjuvant treatments were balanced between groups. Eighty-four patients (Group A: 45, Group B: 39) who completed a one-year follow-up were included in the efficacy analysis and no difference was observed in the RFS between groups (p=0.3). In the subgroup of patients who did not receive adjuvant treatments, we found a significant difference in favor of an INAIC (p=0.009) and an 80% reduction in the risk of early recurrences (Hazard Ratio: 0.20; 95% confidence interval: 0.05-0.81; p=0.0024). No differences were observed in adverse events. Only 4 patients did not receive an INAIC despite being planned. CONCLUSIONS: In this interim analysis, although we could not demonstrate a reduction in the RFS of all patients, we did find a significant decrease of recurrences in patients who did not receive adjuvant treatments. The administration of an INAIC seems to be safe and our protocol appears feasible and reproductive.	bladder
Consumption of Fruits, Vegetables and Bladder Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.	We examined the association between fruit/vegetable consumption and bladder cancer (BC) risk in a systematic review and meta-analysis of prospective cohort studies stratifying results by gender, smoking status and geographical region. Eligible studies were sought in MEDLINE and EMBASE up to April 20, 2020. Random-effects (DerSimonian-Laird) models were implemented for the calculation of pooled relative risks (RRs) and 95% confidence intervals (CI). Fifteen eligible studies were identified (1,993,881 subjects, 11,097 BC cases). Vegetable consumption (pooled RR = 0.95, 95% CI: 0.87-1.04, n = 10) as well as combined fruit/vegetable consumption was not associated with BC risk. Regarding fruit intake, the overall protective trend did not reach significance (pooled RR = 0.91, 95%CI: 0.81-1.02, n = 11); we found however a significant association in East Asians. A trend toward a protective association with citrus fruit consumption was also noted (pooled RR = 0.83, 95%CI: 0.69-1.01, n = 6), once again with a significant effect in East Asians. Moreover, no association was found regarding the subgroups of leafy vegetables, dark green vegetables, and berries. Single studies pointed to a reduced BC risk in never smoking males consuming cruciferous vegetables and East Asians consuming yellow vegetables. In conclusion, our study reveals possible protective effects; larger studies are needed to investigate the emerging trends.	bladder
Role of Pentacyclic Triterpenoid Acids in the Treatment of Bladder Cancer.	Bladder cancer carries a poor prognosis and has proven resistance to chemotherapy. Pentacyclic Triterpenoid Acids (PTAs) are natural bioactive compounds that have a well-known impact on cancer research because of their cytotoxic and chemopreventive activities. This review focuses on bladder cancer which can no longer be successfully treated by DNA damaging drugs. Unlike most of the existing drugs against bladder cancer, PTAs are non-toxic to normal cells. Collecting findings from both in vitro and in vivo studies, it has been concluded that PTAs may serve as promising agents in future bladder cancer therapy. In this review, the roles of various PTAs in bladder cancer have been explored, and their mechanisms of action in the treatment of bladder cancer have been described. Specific PTAs have been shortlisted from each of the chief skeletons of pentacyclic triterpenoids, which could be effective against bladder cancer because of their mode of action. This review thereby throws light on the multi targets and mechanisms of PTAs, which are responsible for their selective anticancer effects and provides guidelines for further research and development of new natural antitumor compounds.	bladder
Intravesical Pseudomonas aeruginosa mannose-sensitive Hemagglutinin vaccine triggers a tumor-preventing immune environment in an orthotopic mouse bladder cancer model.	Bacillus Calmette-Guerin (BCG) immunotherapy can prevent recurrence and progression in selected patients with non-muscle-invasive bladder cancer (NMIBC); however, significant adverse events and treatment failure suggest the need for alternative agents. A commercial anti-infection vaccine comprises a genetically engineered heat-killed Pseudomonas aeruginosa (PA) expressing many mannose-sensitive hemagglutination (MSHA) fimbriae, termed PA-MSHA, which could be a candidate for bladder cancer intravesical therapy. In an immunocompetent orthotopic MB49 bladder cancer model, we characterized the antitumor effects and mechanisms of PA-MSHA compared with those of BCG. Three weekly intravesical PA-MSHA or BCG treatments reduced tumor involvement; however, only PA-MSHA prolonged survival against MB49 implantation significantly. In non-tumor-bearing mice after treatment, flow-cytometry analysis showed PA-MSHA and BCG induced an increased CD4/CD8 ratio, the levels of effector memory T cell phenotypes (CD44, CXCR-3, and IFN-γ), and the proportion of CD11b(+)Ly6G(-)Ly6C(-)IA/IE(+) mature macrophages, but a decrease in the proportion of CD11b(+)Ly6G(-)Ly6C(+)IA/IE(-) monocytic myeloid-derived suppressor cells (Mo-MDSCs) and the expression of suppressive molecules on immune cells (PD-L1, PD-1, TIM-3, and LAG-3). Notably, PA-MSHA, but not BCG, significantly reduced PD-1 and TIM-3 expression on CD4(+) T cells, which might account for the better effects of PA-MSHA than BCG. However, in tumor-bearing mice after treatment, the increased proportion of Mo-MDSCs and high expression of PD-L1 might be involved in treatment failure. Thus, modulating the balance among adaptive and innate immune responses was identified as a key process underlying PA-MSHA-mediated treatment efficacy. The results demonstrated mechanisms underlying intravesical PA-MSHA therapy, pointing at its potential as an alternative effective treatment for NMIBC.	bladder
Risk and prognosis of secondary bladder cancer after post-operative radiotherapy for gynecological cancer.	The aim of this study was to investigate the impacts of radiation therapy (RT) on the occurrence risk of secondary bladder cancer (SBC) and on the patients' survival outcome after being diagnosed with gynecological cancer (EC). The data was obtained from the SEER database between 1973 and 2015. Chi-squared test was used to compare the clinicopathological characteristics among the different groups. Fine and Gray's competing risk model was used to assess the cumulative incidence and occurrence risk of SBC in GC survivors. Kaplan-Meier method was utilized for survival analysis. A total of 123,476 GC patients were included, among which 31,847 (25.8%) patients received RT while 91629 (74.2%) patients did not. The cumulative incidence of SBC was 1.59% or 0.73% among patients who had received prior GC specific RT or not, respectively. All EBRT (standardized incidence ratio (SIR) =2.49, 95% CI [2.17-2.86]), brachytherapy (SIR =1.96, 95% CI [1.60-2.38]), and combinational RT modality groups (SIR =2.73, 95% CI [2.24-3.28]) had dramatically higher SBC incidence as compared to the US general population. Receiving EBRT (HR = 2.83, 95% CI [2.34-3.43]), brachytherapy (HR = 2.17, 95% CI [1.67-2.82]), and combinational RT modality (HR = 2.97, 95% CI [2.34-3.77]) were independent risk factors for SBC development. Survival detriment was observed in SBC patients who received RT after GC diagnosis, as compared to those who did not receive RT. In conclusion, patients who underwent RT after GC had an increased risk of developing bladder as a secondary primary cancer. A long-term surveillance for SBC occurrence is necessary for GC patients who have received prior RT.	bladder
Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells.	Ferroptosis is a form of regulated cell death that emerges to be relevant for therapy-resistant and dedifferentiating cancers. Although several lines of evidence suggest that ferroptosis is a type of autophagy-dependent cell death, the underlying molecular mechanisms remain unclear. Fin56, a type 3 ferroptosis inducer, triggers ferroptosis by promoting glutathione peroxidase 4 (GPX4) protein degradation via a not fully understood pathway. Here, we determined that Fin56 induces ferroptosis and autophagy in bladder cancer cells and that Fin56-triggered ferroptosis mechanistically depends on the autophagic machinery. Furthermore, we found that autophagy inhibition at different stages attenuates Fin56-induced oxidative stress and GPX4 degradation. Moreover, we investigated the effects of Fin56 in combination with Torin 2, a potent mTOR inhibitor used to activate autophagy, on cell viability. We found that Fin56 synergizes with Torin 2 in cytotoxicity against bladder cancer cells. Collectively, our findings not only support the concept that ferroptosis is a type of autophagy-dependent cell death but imply that the combined application of ferroptosis inducers and mTOR inhibitors is a promising approach to improve therapeutic options in the treatment of bladder cancer.	bladder